The SEA domain has been named after the first three proteins in which it was identified (Sperm protein, Enterokinase and Agrin). The SEA domain has around 120 residues, it is an extracellular domain found in a number of cell surface and secreted proteins in which it could be present in one or two copies [ PUBMED:27977898 … expand

The SEA domain has been named after the first three proteins in which it was identified (Sperm protein, Enterokinase and Agrin). The SEA domain has around 120 residues, it is an extracellular domain found in a number of cell surface and secreted proteins in which it could be present in one or two copies [ PUBMED:27977898 ]. Many SEA domains possess autoproteolysis activity. The SEA domain is closely associated with regions receiving extensive O-glycosylation and is present adjacent to the transmembrane segment in quite a number of type I transmembrane proteins on the cell surface, such as mucin-1 (MUC1) and Notch receptors and in type II single-pass transmembrane proteins such as enterokinase and matriptases. It also present in interphotoreceptor matrix proteoglycans (IMPG1 and IMPG2) [ PUBMED:27977898 ]. It has been proposed that carbohydrates are required to stabilise SEA domains and protect them against proteolytic degradation and that the extent of substitution may control proteolytic processing [ PUBMED:7670383 PUBMED:9762901 ].

The SEA domain contains an about 80-residue conserved region and an about 40-residue segment that separates the conserved region from the subsequent C-terminal domains with an alternating conformation of β-sheets and α-helices. Structural analysis of MUC1 SEA domain revealed that it adopts a ferredoxin-like fold in which the cleavage site is located in the middle of the β-hairpin of the second and third β-strands. MUC1 SEA domain undergoes autoproteolysis at the glycine-serine peptide bond and the Ser responsible of this activity is located in the consensus motif GSXXX (X: a hydrophobic residue) [ PUBMED:27977898 PUBMED:7670383 PUBMED:9030729 ].

Some proteins known to contain a SEA domain include:

• Vertebrate agrin, an heparan sulfate proteoglycan of the basal lamina of the neuromuscular junction. It is responsible for the clustering of acetylcholine receptors (AChRs) and other proteins at the neuromuscular junction.
• Mammalian enterokinase. It catalyses the conversion of trypsinogen to trypsin which in turn activates other proenzymes, including chymotrypsinogen, procarboxypeptidases, and proelastases.
• 63kDa sea urchin sperm protein (SP63). It might mediate sperm-egg or sperm-matrix interactions.
• Animal perlecan, a heparan sulfate containing proteoglycan found in all basement membranes. It interacts with other basement membrane components such as laminin and collagen type IV and serves as an attachment substrate for cells.
• Some vertebrate epithelial mucins. They form a family of secreted and cell surface glycoproteins expressed by epithelial tissues and implicated in epithelial cell protection, adhesion modulation and signaling.
• Mammalian cell surface antigen 114/A10, an integral transmembrane protein that is highly expressed in hematopoietic progenitor cells and IL-3-dependent cell lines.